A peptic ulcer refers to a condition in which partially lost epithelia have spread deep inside the mucosal lining of the gastrointestinal tract. Causes of ulcer development are generally considered to be explained based on the balance theory that an ulcer is induced due to a loss of balance between the functions of aggressive factors such as gastric acid, pepsin, stress, Helicobacter pylori (hereinafter referred to as “H. pylori”), and nonsteroidal anti-inflammatory drugs (hereinafter referred to as “NSAID”) and those of protective factors for gastrointestinal mucosa, i.e., mucus and mucosal barriers, blood flow and microcirculation, growth factors, and prostaglandin.
Major peptic ulcers include gastric ulcers and duodenal ulcers.
Gastric ulcers are caused mainly by weakened defense mechanisms for gastric mucosa. Infection with H. pylori, NSAID, and stress weaken the defense mechanisms to cause damage to gastric mucosa, which progresses into an ulcer. Duodenal ulcers are caused by increased secretion of gastric acid, which causes damage to duodenal mucosa, which is vulnerable to attack by gastric acid. Infection with H. pylori also weakens duodenal mucosa. High-fat diets and the like lead to increased secretion of gastric acid.
The three most common causes of gastric and duodenal ulcers are infection with H. pylori, nonsteroidal anti-inflammatory drugs (NSAID), and stress.
Among these causes, stress such as social stress may result in a stress-induced ulcer, which is mainly caused by psychological stress. It is desirable to develop a prophylactic drug for stress-induced ulcers, the drug capable of being administered, in daily living, to those in an environment where they are susceptible to psychological stress and those prone to have psychological stress without side effects.
It is also desirable to develop prophylactic and therapeutic agents that can be used for a peptic ulcer caused by H. pylori or NSAID rather than psychological stress and that have no side effects.
It has been reported that if a patient in an intensive care unit has two risk factors: controlled artificial respiration for 48 hours or longer and a clotting disorder, the patient has an increased risk for clinically-significant gastrointestinal bleeding and has increased mortality. Thus, if a patient in an intensive care unit has these two risk factors, a PPI (proton pump inhibitor) or an H2RA (histamine 2 receptor antagonist) for prevention of a stress-induced gastrointestinal ulcer is typically administered to provide preventive treatment of a stress-induced ulcer and bleeding (for example, Non Patent Literature 1).